Naltrexone is an orally-administered opioid antagonist with the chemical name morphinan-6-one,17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxy-(5α).
The molecular formula of naltrexone is C20H23NO4 and its molecular weight is 341.41 in the anhydrous form (<1% maximum water content). The chemical structure of naltrexone is shown below.

Naltrexone is commonly used as a treatment for opiate addiction. A number of patients, however, use low doses of naltrexone (LDN) as an off-label treatment for a range of immune-related pathologies and cancer. There is preliminary evidence that LDN may be effective in Multiple Sclerosis (Rahn et al. 2011), Crohn's disease (Smith et al. 2011) and certain cancers.
With regard to cancer, Zagon and McLaughlin (1983) and Hytrek et al. (1996) reported LDN-mediated inhibition of murine neuroblastoma and human colon cancer cell growth respectively, when evaluated in murine xenograft models. Furthermore, combinations of LDN with additional therapeutic agents have been found to be effective against the growth and progression of certain cancer types, for example Donahue et al. (2011a) reported potent anti-proliferative effects of LDN and cisplatin on human ovarian cancer cells both in vitro and in an in vivo murine xenograft model. In the clinic, Berkson et al. (2006) described the long term survival of a patient having pancreatic cancer with metastasis to liver, following treatment with α-lipoic acid in combination with LDN; the authors have since reported similar observations in three further patients with metastatic pancreatic cancer (Berkson et al. 2009).
The role of LDN in the above observations has so far largely been explained by reference to the antagonistic action of LDN on the opioid growth factor receptor (OGFr). OGFr recognises opioid growth factor (OGF, also referred to as [Met5]-enkephalin), and intermittent doses of naltrexone appear to provide a temporary blockade that triggers upregulation of the receptor (Hytrek et al. 1996). This upregulation of OGFr has been found to result in decreased in vitro proliferation of cells representative of pancreatic, colorectal and squamous cell carcinomas (Donaghue et al. 2011 b).
However, a potential mechanism for LDN as a direct immunomodulator has been revealed in studies by Hutchinson et al. (2008), who demonstrated that in addition to its effects on OGFr, naltrexone can weakly antagonise TLR4, a member of the Toll-like receptor (TLR) family. Pattern recognition receptors such as TLRs allow immune cells to detect the presence of pathogens or self-derived danger signals, and instruct them to trigger an immune response. Innate immune activation is a necessary step for eliciting subsequent adaptive immune responses, and given the powerful inflammatory potential of TLRs, their activity must be tightly controlled. In general, TLR stimulation elicits the induction of feedback mechanisms, but when this fails, TLR overactivity can lead to inappropriate immune responses, immune exhaustion and/or autoimmunity.